The general objective is to take advantage of the fact that mammalian nonmyelinated fibers, being small, have a larger amount of axonal membrane per gram of tissue than do myelinated fibers or squid giant axons. These fibers are therefore particularly suited to metabolic studies and to the changes in intracellular ion concentrations with electrical activity since much of the physiology of nerve cells concern events that happen at the axolemma. Furthermore, mammalian non-myelinated nerves possess a set of receptor sites for which the lithium ion has a relatively high-affinity (K=2-4 mM) and reduces the efflux of inorganic phosphate. Since lithium is thus effective in this system in the range of concentration used therapeutically experiments will be done to characterize this site. The non-myelinated fibers are enveloped by Schwann cells; and in cross-section the area of Schwann cell cytoplasm is about the same as that of the axons. One general objective of the present work is to determine how much the Schwann cells contribute to the biophysical and the electrophysiological properties of non-myelinated fibers by studying separately both non-myelinated fibers free of Schwann cells and primary cultures of Schwann cells free of axons. Electrophysiologically, the axons will be studied by the sucrose gap method and the Schwann cells by the patch-clamp method. Measurements will also be made of phosphate fluxes from both systems and of the effects on these fluxes of various neurohumors (such as acetylcholine and lithium). The sodium channel density of each will be determined by saxitoxin binding assays and the relative contribution of each to the binding of the whole nerve assessed. In another series of experiments the large surface- volume ratio will again be taken advantage of in an attempt to study the effect of nerve degeneration following a crush and subsequent regeneration in the sodium channel density (measured by labelled STX binding). In addition, the sensitivity of the compound action potential to 4-AP will be used to test for the presence of potassium channels, and to elucidate changes in regenerating non-myelinating nerve.